Overexpression of Notch1 is associated with the progression of cervical cancer

Sun, Yan; Zhang, Rui; Zhou, Shujuan; Ji, Yibing

doi:10.3892/ol.2015.3143

Cited by 20 publications

(21 citation statements)

References 36 publications

(37 reference statements)

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“…A previous report showed that the G1393A (p.A465T) mutation leads to a conformational change of NOTCH1 ligand-binding domain by protein structure simulation (16). However, recent studies using cancer cell lines could not provide evidence about the functional role of NOTCH1 mutations detected in clinical samples (15,19,20). Thus, to clarify the function of NOTCH1 in OSCC, we established A465T cells expressing the NOTCH1 A465T mutant and examined its characteristics.…”

Section: Discussionmentioning

confidence: 98%

A mutation in NOTCH1 ligand binding region detected in patients with oral squamous cell carcinoma reduces NOTCH1 oncogenic effect

et al. 2017

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NOTCH1 is known as an oncogenic or tumor suppressive gene in solid cancer. NOTCH1 mutations in oral squamous cell carcinoma (OSCC) frequently occur near the ligand-binding region. These mutations change the domain structure of this protein and affect the ligand binding activity. When NOTCH1 is activated by ligand binding, NOTCH1 intracellular domain (NICD) is cleaved from the cell membrane. This study investigated the functional change induced by a NOTCH1 mutation detected in OSCC clinical samples using stable transformant analysis. HEK293 cell lines expressing NOTCH1 wild-type (WT cells) or p.A465T NOTCH1 (A465T cells) were established. NOTCH1 expression was analyzed by flow cytometry, western blotting, and immunofluorescence using an anti-human NOTCH1 antibody. mRNA expression levels in WT and A465T cells were determined by quantitative real-time PCR (qPCR). Cell proliferation was analyzed by using cell growth assays and a xenograft tumor assay. Flow cytometry indicated that NOTCH1 expression on the cell membrane was lower in A465T cells than that in WT cells. NOTCH1 and NICD were both detected by western blot in WT and A465T cells. The immunofluorescence signal for NICD was detected in the nucleus of WT cells, while it was localized mainly in the cytoplasm of A465T cells. HES1 and HEY1 mRNA expression levels were lower in A465T than in WT cells. The cell growth of WT cells was significantly higher than that of HEK293 cells (3-fold, P<0.01), while that of A465T cells was significantly lower than that of HEK293 cells (37%, P<0.01). In a xenograft model, the tumor cell implantation rate of WT cells was 80%, while that of A465T cells was 0%. This study indicates that NOTCH1 acts as an oncogene and that the NOTCH1 mutation (p.A465T) in the ligand-binding region causes the loss of tumorigenicity by downregulating the NOTCH1 pathway.

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Section: Discussionmentioning

confidence: 98%

A mutation in NOTCH1 ligand binding region detected in patients with oral squamous cell carcinoma reduces NOTCH1 oncogenic effect

et al. 2017

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“…Therefore, it is possible to diagnose cervical cancer based on the activity of telomerase and predict the development of cervical cancer. In summary, p16 INK4a , Notch1, and hTERC genes are abnormally expressed in HPV‐infected cervical diseases . However, there are large differences in the reports of p16 INK4a ‐positive expression rates in cervical tissues in different articles .…”

Section: Introductionmentioning

confidence: 91%

Relevance research between the expression of p16^INK4a, Notch1, and hTERC genes: The development of HPV16‐positive cervical cancer

Huo

Zhai

Wang

et al. 2020

Clinical Laboratory Analysis

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Background: GLOBOCAN 2018 latest data show cervical cancer ranks fourth in morbidity and mortality among women. Many genes in cervical lesions differ in sensitivity and specificity. However, the diagnostic molecules for early cervical cancer are not very clear. This paper screens biomarkers for early molecular diagnosis of Mongolian patients with cervical cancer. Methods: Immunohistochemical SP method was used to detect the expression of p16 INK4a and Notch1 protein in paraffin sections of 226 Mongolian patients with HPV16-positive cervical lesions after pathological examination, and 100 of them were randomly selected by fluorescence in situ hybridization to detect hTERC gene. The HPV16-binding human cervical cancer SiHa cell line was used to silence the expression of HPV16 E6/E7 gene by RNA interference, and the expression of p16 INK4a , Notch1, and hTERC genes and protein expression levels were detected by RT-PCR and Western blot.Results: The positive expression rates of p16 INK4a , Notch1, and hTERC genes in HPV16-positive cervical cancer, CIN-III, CIN-II, CIN-I, uterine leiomyoma, and chronic cervicitis were significantly different (P < .05); the positive expression rates of the three genes were also significantly different in the same type of cervical lesions (P < .05); RNA interference can effectively inhibit HPV16 E6/E7, p16 INK4a and Notch1 gene expression, but has no effect on hTERC gene expression.

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“…Furthermore, the role of Notch 1 played different roles in different stages of tumor development. For instance, it promoted tumor development in early-stage of cervical cancer and suppressed tumor development in late-stage cervical cancer [39][40][41]. Whether the carcinogenesis of C3orf21 overexpression was dependent on specific tissue context, microenvironment, and crosstalk with other signaling pathways needs further elucidation.…”

Section: Issues and Perspectivesmentioning

confidence: 99%

C3orf21 and Notch Signaling in Cancer：A Potential Biomarker

Zhang¹,

Dehou²,

Bao³

2018

Int J Pathol Clin Res

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C3orf21 (chromosome 3 open reading frame 21), also known as xyloside xylosyltransferase 1 (XXYLT1), is located on chromosome 3q29. C3orf21 belongs to the glycosyltransferase 8 family, furthermore, it is a retaining glycosyltransferase. In the extracellular domain of target proteins, XXYLT1 catalyzes addition of the second sylose, and then elongates the O-linked xylose-glucose disaccharide attached to EGF-like repeats. XXYLT1 negatively regulates Notch signaling, and aberrations in the Notch signaling pathway were associated with a few types of cancers. So, C3orf21 must be associated with cancer development. Our previous research has found that the C3orf21 polymorphisms were associated with lung cancer risk, and the ablation of C3orf21 gene (XXYLT1) promoted lung cancer MSTO-211H cell proliferation, inhibited apoptosis and accelerated cell migration. Understanding the role of C3orf21 in the cancer development may provide insights into the potential of C3orf21 as a cancer biomarker. Here, we reviewed several representative studies for understanding the C3orf21 and Notch signaling in cancer.

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Overexpression of Notch1 is associated with the progression of cervical cancer

Cited by 20 publications

References 36 publications

A mutation in NOTCH1 ligand binding region detected in patients with oral squamous cell carcinoma reduces NOTCH1 oncogenic effect

A mutation in NOTCH1 ligand binding region detected in patients with oral squamous cell carcinoma reduces NOTCH1 oncogenic effect

Relevance research between the expression of p16^INK4a, Notch1, and hTERC genes: The development of HPV16‐positive cervical cancer

C3orf21 and Notch Signaling in Cancer：A Potential Biomarker

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Overexpression of Notch1 is associated with the progression of cervical cancer

Cited by 20 publications

References 36 publications

A mutation in NOTCH1 ligand binding region detected in patients with oral squamous cell carcinoma reduces NOTCH1 oncogenic effect

A mutation in NOTCH1 ligand binding region detected in patients with oral squamous cell carcinoma reduces NOTCH1 oncogenic effect

Relevance research between the expression of p16INK4a, Notch1, and hTERC genes: The development of HPV16‐positive cervical cancer

C3orf21 and Notch Signaling in Cancer：A Potential Biomarker

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Relevance research between the expression of p16^INK4a, Notch1, and hTERC genes: The development of HPV16‐positive cervical cancer